Despite the very high prevalence of female pelvic floor disorders (urinary incontinence, fecal incontinence, and pelvic organ prolapse), the biological mechanisms underlying these disorders are uncertain. Epidemiologic studies suggest that childbirth plays an essential role. The long-term research goals of this team are to identify specific obstetrical events associated with pelvic floor disorders and to investigate the biologica mechanisms underlying these associations. In the first period of this award, pelvic floor disorders were shown to be significantly increased after vaginal versus cesarean birth at a single point in time, 5-10 years after first childbirth. Also, pelvic muscle strength was found to e significantly poorer after vaginal versus cesarean birth. Recognizing the critical influence of obstetrical events on the biological pathways leading to pelvic floor disorders, the goals of this proposal are to describe changes over time in pelvic floor disorders and to investigate the extent to which these changes are affected by childbirth and by pelvic muscle weakness. The specific aims of the current application are: AIM 1: to investigate the effect of obstetrical exposures on the incidence and progression of pelvic floor disorders and AIM 2: to investigate the effect of pelvic muscle weakness on the progression of pelvic floor disorders. These aims will be accomplished via annual surveillance of an established cohort of >1300 parous women (plus additional participants recruited annually). Using data from validated questionnaires and physical examinations, the severity of pelvic floor disorders will be measured annually. The exposures of interest will include obstetrical events (vaginal versus cesarean birth, forceps delivery, episiotomy and perineal laceration) and pelvic muscle strength (measured in this cohort at the end of the first funding cycle, using a validated tool). Analysis will focus on factos associated with disease progression over time as well as the prognosis for women with mild pelvic floor disorders. Novel aspects of this research include the focus on measures of disease severity over time, analytical methods that consider heterogeneity of effect, and the opportunity to prospectively examine the impact of pelvic muscle weakness. The proposed research is significant because it will provide critical information about the natural history of pelvic floor disorders and identify the most important obstetrical antecedents. Thus, the findings will identify women at greatest risk for pelvic floor disorders and will serve as a foundation for prevention trials. Also, pelvic muscle weakness may prove to be a novel target for therapeutic intervention. Finally, results are expected to advance science by guiding future translational research on pathophysiology of pelvic floor disorders. Given the high prevalence of pelvic floor disorders and the high incidence of surgical treatment for these conditions, prevention is critical to reduce the public health burden of pelvic floor disorders among U.S. women.